Many transporting and secreting tissues exhibit transient increases of cAMP as well as cGMP levels following stimulation. Thus, there are reasons to expect that the same kind of behaviour would occur in the gastric mucosa, when it is stimulated. At the present time little attention has been given the non-steady state gastric mucosa and consequently the temporal relationship between cyclic nucleotides and acid secretion is inadequately understood. The objective of this study is to elucidate the time relationship between changes in adenine nucleotides and acid secretion in intact isolated frog gastric mucosa. Preliminary data obtained by my use of this preparation indicates that early events following histamine stimulation include transient increases in cAMP and ATP levels. The change in cAMP precedes that of ATP and both precede the onset of acid secretion. The data also indicate a rise in total adenine nucleotides and suggest that the observed unchanged levels of ATP and elevated levels of ADP during acid secretion are due to increased intracellular pH. In the present study I propose to measure in more detail the relationship between adenine nucleotides, acid secretion and electrical variables as a function of time in resting and histamine stimulated gastric mucosa. The possible role of cAMP-dependent protein kinase in acid secretion will be investigated including a study of the effects of phosphodiesterase inhibitors and H2-antagonists on cAMP and cAMP-dependent protein kinase. The effect of other secretagogues such as pentagastrin and acetylcholine on cAMP and cGMP and protein kinases will also be studied.